Impact of Mesenchymal Stem Cell Senescence on Inflammaging

Abstract

Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptiveimmunity and develops a persistent and mild systemic inflammation, inflammaging. With their unique therapeutic properties, such as immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs) have been considered to be a promising source for treating autoimmune disease or as anti-aging therapy. Although direct evidence of the role of MSCs in inflammaging has not been thoroughly studied, features reported in senescent MSCs or the aging process of MSCs are associated with inflammaging; MSC niche-driven skewing of hematopoiesis toward the myeloid lineage or oncogenesis, production of pro-inflammatory cytokines, and weakening their modulative property on macrophage polarization, which plays a central role on inflammaging development. This review explores the role of senescent MSCs as an important regulator for onset and progression of inflammaging and as an effective target for anti-aging strategies. [BMB Reports 2020; 53(2): 65-73] BMB Rep. 2020; 53(2): 65-73

Age-related cerebral small vessel disease and inflammaging

“…d. MSC is one of the critical components of the hematopoietic stem cell (HSC) niche, which plays a crucial role in maintaining HSC homeostasis and bone marrow microenvironment. Age-associated mutations hinder niche functions of MSCs and compromise their hematopoietic supportive function in the elderly 19 .…”

Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties

“…In addition, TSG-EV significantly increased the expression level of anti-inflammatory factors such as TGFβ, COX-2 and IDO. Importantly, the expression levels of pro-inflammatory factors (IFNγ, TNFα, and IL-1β) were decreased or remained similar in TSG-EV, suggesting that TSG-induced EV release had a different secretory mechanism from that of inflammaging or senescence-associated secretory phenotype (SASP) of MSCs [ 48 ]. Especially, TSG-EV showed ~15 fold higher IDO level compared to CTL-EV, which is a critical regulator of colitis-related inflammation through development of regulatory T cells and M2-type macrophages [ 6 , 49 ].…”

Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application

“…Although the age of the donor seems to be less crucial for specific properties such as tenogenic potential [ 6 ], MSCs from aged donors generally present lagged capability in proliferation, differentiation, and immunoregulation; subsequently, aged cells showed impaired therapeutic outcomes in the disease model [ 7 ]. The infusion of aged MSC would rather deteriorate the disease severity by causing “inflammaging” in the body of recipients [ 8 ]. Senescent cells are known to display a senescence-associated secretory phenotype (SASP) that contributes to the progress of aging of neighboring cells, impaired regenerative function, and immune cell recruitment after administration [ 9 ].…”